Glycoluril is a bicyclic molecule which is used for the preparation of supramolecular hosts, i.e. molecules that are able to bind other molecules (guests) through non-covalent interactions. There are several examples of glycoluril based supramolecular hosts. Nolte and co-workers described glycolurils terminated by xylylene units which are able to self-assembly into dimeric aggregates and/or to form host-guest complexes with small molecules (Rowan, A. E.; Elemans, J. A. A. W.; Nolte, R. J. M. Acc. Chem. Res. 1999, 995-1006). Rebek and co-workers prepared molecules, in which terminal glycoluril units are connected through various spacers. These molecules are able to self-associate in non-polar solvents into spherical structures. These structures are stabilized by N —H . . . O hydrogen bonds which are formed between terminal glycoluril units (Rebek, J., Jr. Acc. Chem. Res. 1999, 32, 278-286). Singh et al. (U.S. Pat. No. 5,298,539 to Cytec Industries) describes additives for improving tire cord adhesion and toughness of vulcanized rubber compositions, containing linear oligomers of glycoluril units connected directly by N—N bond.
Among the glycoluril based supramolecular hosts, most attention is paid to cyclic glycoluril oligomers called cucurbit[n]urils in which n glycoluril units are connected through 2n methylene bridges (Lagona, J.; Mukhopadhyay, P.; Chakrabarti, S.; Isaacs, L. Angew. Chem., Int. Ed. 2005, 44, 4844-4870). Cucurbit[6]uril, the first member of the cucurbituril family, was prepared in 1905 (Behrend, R; Meyer, E; Rusche, F. Liebigs Ann. Chem. 1905, 339), but its macrocyclic structure was not discovered until 1981 (Freeman, W. A.; Mock, W. L.; Shih, N.-Y. J. Am. Chem. Soc. 1981, 103, 7367). In the beginning of the 21st century two research groups led by K. Kim and A. Day independently described the preparation and isolation of cucurbit[n]urils in which the number of glycoluril units n varies in the range from 5 to 10 (A. I. Day, A. P. Arnold, R. J. Blanch (Unisearch Limited, Australia), WO2000068232. Day, A.; Arnold A. P.; Blanch, R. J.; Snushall, B. J. Org. Chem. 2001, 66, 8094. K. Kim, J. Kim, I.-S. Jung, S.-Y. Kim, E. Lee, J.-K. Kang (Postech Foundation, South Korea), EP1094065. Kim, J.; Jung, I.-S.; Kim, S. Y.; Lee, E.; Kang, J.-L.; Sakamoto, S.; Yamaguchi, K.; Kim, K. J. Am. Chem. Soc. 2000, 122, 540). Recently it was also demonstrated that the choice of suitable reaction conditions allows for the preparation of CB analogs such as diastereomeric inverted cucurbit[n]urils (Isaacs, L.; Park, S.-K.; Liu, S.; Ko, Y. H.; Selvapalam, N.; Kim, Y.; Kim, H.; Zavalij, P. Y.; Kim, G.-H.; Lee, H.-S.; Kim, K. J. Am. Chem. Soc. 2005, 127, 18000-18001.), bis-ns cucurbit[10]uril (Huang, W.-H.; Liu, S.; Zavalij, P. Y.; Isaacs, L. J. Am. Chem. Soc. 2006, 128, 14744-14745), and/or (±)-bis-ns-cucurbit[6]uril (Huang, W.-H.; Zavalij, P. Y.; Isaacs, L. Angew. Chem., Int. Ed. 2007, 46, 7425-7427). Using the same approach, Isaac's group has been able to isolate acyclic oligomers with the number of glycoluril units ranging from 2 to 6 (Huang, W.-H.; Zavalij, P. Y.; Isaacs, L. J. Am. Chem. Soc. 2008, 130, 8446-8454). Based on the size of its cavity, cucurbit[n]urils are able to form inclusion or exclusion complexes with organic and inorganic guests of various sizes. The binding is selective and the formed supramolecular complexes are characterized by high binding constants. These outstanding properties of cucurbit[n]urils have led to their use in a number of applications including waste stream remediation, controlled drug release, catalysis, sensors, and chromatography.
Cucurbit[n]urils are prepared by acid-catalyzed condensation between glycoluril and formaldehyde. Reaction is carried out in a concentrated mineral acid such as HCl and H2SO4 at temperature above 50° C. (e.g., WO0068232, WO2007106144). The separation of single cucurbit[n]uril homologues from the reaction mixture is time consuming and it is achieved by the combination of fractional crystallization and chromatography techniques. Another limit in cucurbit[n]urils applications is their insolubility in organic solvent. Also the solubility of cucurbit[n]urils in water is low, but it increases in the presence of metal or organic cations. Due to their rigid structure cucurbit[n]uril macrocycles are very difficult to modify.
In 2004 the preparation of new macrocyclic compounds based on ethyleneurea and formaldehyde were published (Miyahara, Y.; Goto, K.; Oka, M.; Inazu, T. Angew. Chem., Int. Ed. 2004, 43, 5019-5022). The structure of this macrocycle resembles the structure of cucurbit[n]uril which is cut in half along the equator. Therefore the authors named these new compounds hemicucurbit[n]urils (wherein n=6 and 12). In contrast to cucurbit[n]urils, hemicucurbit[n]urils are soluble in non-polar solvents. However they are capable of forming complexes with a limited range of anions, and these complexes have a relatively low association constant.
As we described above, macrocyclic molecules based on glycoluril are promising compounds which can act as supramolecular hosts. Low solubility and limited modificability represent basic drawback for their further application.
New class of glycoluril based compounds which eliminates the disadvantages of known glycoluril macrocyclic compounds is the object of the present invention.